摘要
目的探讨三七总皂苷(PNS)对顺铂肾损伤模型肾组织自噬保护的可能机制。方法将大鼠随机分为正常对照组,顺铂模型组,顺铂+PNS组,在给药4和8 d后分别处理大鼠,检测尿β-N-乙酰胺基葡萄糖苷酶(NAG)、血清尿素氮(BUN)和肌酐(Cr)的水平,同时利用透射电子显微镜(TEM)观察肾小管上皮细胞线粒体及自噬体的形态学变化,通过Western blotting检测自噬蛋白LC3、HIF-1α、BNIP3及Beclin1蛋白的表达。结果大鼠分别给药4和8 d后,PNS明显降低了顺铂肾损伤大鼠的尿NAG,血清BUN和Cr水平(P<0.05)。此外,PNS干预顺铂肾损伤大鼠4和8 d后,肾组织LC3、HIF-1α、BNIP3及Beclin1蛋白表达水平明显升高(P<0.05),同时减轻了肾上皮细胞线粒体的损伤。PNS干预顺铂肾损伤大鼠8 d后,肾功能和蛋白表达水平的改变均比干预4 d后显著(P<0.05)。结论 PNS可能通过HIF-1α/BNIP3途径增强顺铂肾损伤模型肾组织的线粒体自噬水平起保护作用;随着PNS的干预时间延长,其对大鼠肾损伤的肾组织的保护作用增强。
OBJECTIVE To investigate the possible mechanism of Panax notoginseng saponins （PNS） protection against cispla- tin-induced kidney injury through enhangcing autophagy. METHODS The rats were randomly divided into normal control group, cis- platin model group and cisplatin ＋ PNS group. After exposure to cisplatin for 4 and 8 d, the urinary β-N-acetyl-β-D-glucosaminidase （NAG）, blood urea nitrogen （BUN） and serum creatinine （Scr） were measured by commercial kits, and the pathological change of renal tissue was examined using transmission electron microscopy. Additionally, the expression of LC3, HIF-1α, BNIP3 and Beclinl were examined by Western blotting. RESULTS PNS decreased the levels of urinary NAG, serum BUN and Scr which were increased by cisplatin （P 〈 0.05）. Moreover, PNS significantly increased the expression of LC3, HIF-1 α, BNIP3 and Beclinl （P 〈 0. 05 ）, and attenuated the mitochondrial damages of renal cells. Furthermore, the effects of PNS on the mentioned above were more obvious at day 8 than that at day 4 （P 〈 0. 05）. CONCLUSION PNS may play a protective role against cisplatin-induced kidney injury with certain of time dependence, by enhancing mitochondrial autophagy in rat renal tissue via the HIF-1α/BNIP3 pathway.
作者
周金玲
杨玉芳
黄振光
邹小琴
梁雪艳
ZHOU Jin-ling YANG Yu-fang HUANG Zhen-guang ZOU Xiao-qin LIANG Xue-yan(Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2017年第3期196-200,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(81260598
81560729)
